Single-cell transcriptomic atlas of mouse cochlear aging

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.

The circadian timing of noise exposure influences noise-induced inflammatory responses in the mouse cochlea

Abstract Introduction: Noise-induced hearing loss is one of the most common forms of sensorineural hearing loss. Nevertheless, the mechanisms of noise-induced hearing loss are still not fully understood. Objective: To investigate the dynamics of inflammatory responses in the mammalian cochlea following noise trauma at two different times, once during the light cycle and once during the dark. Methods: We challenged C57BL/6J mice with moderate, continuous noise trauma at either 9 a.m. or 9 p.m. Auditory function, histological changes in hair cells, and modifications in gene expression levels of inflammatory mediators were assessed at specific time points. Shifts in auditory brainstem response thresholds were measured at 1, 3, 7 and 14 days after noise exposure to measure potential noise-induced hearing loss. Cochlear basilar-membrane immunofluorescent staining was performed at 3 and 14 days after noise exposure. The mRNA levels of several inflammatory mediators were measured via quantitative real-time polymerase chain reaction before (pre) and after (0, 3, 12, 24 and 72 h) noise exposure. Results: We found that all noise-exposed mice developed a temporary threshold shift and that there were no significant differences between daytime and nighttime noise exposures in terms of inducing hearing-threshold shifts. Similarly, we did not detect significant histological changes in hair cells between these two groups. However, we discovered an interesting phenomenon in that the peak mRNA levels of IL-1β, IL-6, CCL2 and TNF-α were higher in day noise-exposed mice compared to those in night noise-exposed mice, and these mRNA levels subsided more slowly in day noise-exposed mice. Conclusion: Overall, these observations suggest that the circadian timing of noise exposure has a significant effect on noise-induced inflammatory responses in the mouse cochlea and that a greater inflammatory response might occur after daytime exposure.

The Induction of Hypothyroidism during Gestation Decreases Outer Hair Cell Motility in Rat Offspring

Abstract Introduction Perinatal hypothyroidism has a negative repercussion on the development and maturation of auditory system function. However, its long-term effect on auditory function remains unsettled. Objective To evaluate the effect of prenatal hypothyroidism on the auditory function of adult offspring in rats. Methods Pregnant Wistar rats were given the antithyroid drug methimazole (0.02%-1-methylimidazole-2-thiol- MMI) in drinking water, ad libitum, from gestational day (GD) 9 to postnatal day 15 (PND15). Anesthetized offspring from MMI-treated dams (OMTD) and control rats were evaluated by tympanometry, distortion product otoacoustic emission (DPOAE), and auditory brainstem response (ABR) at PNDs 30, 60, 90, and 120. Results Our data demonstrated no middle ear dysfunction, with the OMTD compliance lower than that of the control group. The DPOAE revealed the absence of outer hair cells function, and the ABR showed normal integrity of neural auditory pathways up to brainstem level in the central nervous system. Furthermore, in the OMTD group, hearing loss was characterized by a higher electrophysiological threshold. Conclusion Our data suggest that perinatal hypothyroidism leads to irreversible damage to cochlear function in offspring.

Auditory and Vestibular Functioning in Individuals with Type-2 Diabetes Mellitus: A Systematic Review

Abstract Introduction Diabetes mellitus is a metabolic disease associated with a rise in the level of blood glucose. Individuals with diabetes mellitus are more likely to develop hearing loss, tinnitus, and dizziness due to macro- and microvascular complications. The extent to which auditory and vestibular functions are impaired in individuals with type-2 diabetes mellitus is still under debate. Objective To systematically review studies focusing on auditory and vestibular functions in individuals with type-2 diabetes mellitus. Data Synthesis A search was conducted in the PubMed, MedlinePlus, Ingenta Connect and Google Scholar databases for articles published until June 2019. A total of 15,980 articles were primarily retrieved, 33 of which were shortlisted based on the inclusion criteria set by the investigators for the systematic review. Out of 33 full-length articles, 26 evaluated the functioning of the auditory system, while 7 evaluated the functioning of the vestibular system. Most studies related to auditory functioning reported a significant effect of type-2 diabetes mellitus on the peripheral auditory system, whereas studies on vestibular functioning reported no significant effect of diabetes mellitus on the functioning of the peripheral vestibular end-organ. Conclusion Overall, the results of various audiological and peripheral vestibular tests reveal distinctive peripheral and/or central auditory and vestibular end-organ impairments in individuals with type-2 diabetes mellitus.

Sordera neurosensorial congénita con malformación de oído interno ligada al X en una familia mexicana / Congenital sensorineural deafness X-linked, with inner ear malformation in a Mexican family

Introducción. Las sorderas o hipoacusias prelinguales son de etiología genética entre el 60 y el 68% de los casos; de estos, del 20 al 40% son malformaciones del oído interno. De los casos de hipoacusia no sindrómica ligada al X se han descrito siete tipos. De las malformaciones de oído interno, la partición coclear incompleta tipo III es la menos frecuente.Objetivo. Presentar el reporte clínico-genético de una familia mexicana, con indi-viduos varones afectados por sordera neurosensorial congénita con malformación de oído interno. Material y Métodos. Se realizó estudio de una familia en la que nueve miembros presentaban sordera. Se estudiaron cuatro de ellos y una madre sin manifestaciones, a través del estudio clínico general por médico genetista, el estudio audiológico (otos-copía y audiometría) por médico audiólogo y el estudio de tomografía computada (TC) por médico radiólogo.Resultados. Los pacientes estudiados presentaron sordera neurosensorial congéni-ta, de severa a profunda bilateral. A través de la TC, se evidenció malformación de oído interno. Tres pacientes presentaron partición coclear incompleta tipo III y un paciente partición incompleta tipo I. Debido al estudio clínico y al árbol genealógico, se definió diagnóstico de hipoacusia neurosensorial no sindrómica ligada al X. La TC de la madre sin manifestaciones no presentó evidencia de malformaciones en oído interno (MOI).Conclusión. El estudio de imagen es fundamental para definir presencia o no de MOI en todos los pacientes con hipoacusia y así poder guiar la terapéutica y el aseso-ramiento genético, así como realizar los estudios moleculares más adecuados

Introduction. The pre-lingual deafness or hearing loss are of genetic cause in be-tween 60% and 68% of cases, among these, between 20% and 40% are malforma-tion of the inner ear. From the non-syndromic hearing loss cases that are linked to the X chromosome, seven types have been described. Among these inner ear malforma-tions, incomplete cochlear partition type III is the less frequent.Objective. Present the clinical genetical report of a Mexican family, with male in-dividuals affected by congenital neurosensory deafness with inner ear malformation.Materials and methodology. A study on a family in which nine members were affected by deafness was done. Four of them, plus a mother without manifestation, were studied through a general clinical study by a geneticist, an audiological study (otoscopy and audiometry) by an audiologist, and a computed tomography (CT) scan by a radiologist.Results. The studied patients presented congenital neurosensory deafness, from se-vere to deep bilateral. Via the CT, the inner ear malformation was made clear. Three of the patients presented incomplete cochlear partition type III and one patient in-complete cochlear partition type I. Due to the clinical study and the family tree, it was diagnosed non-syndromic neurosensory deafness linked to X. The CT of the mother without manifestation did not show evidence of inner ear malformations.Conclusion. The study by image is fundamental to define whether there is or not a presence of inner ear malformations in any patient with heading loss to be able to guide the therapeutics and the genetic counseling, as well as to make more accurate molecular studies

Avaliação audiológica em pacientes com hepatite C crônica tratados por antivirais de ação direta / Audiological evaluation in patients with chronic hepatitis C treated by direct-action antivirals

RESUMO Objetivo Verificar se o tratamento com os antivirais de ação direta para a hepatite C provocam efeitos adversos na audição. Métodos A casuística foi composta por 16 indivíduos portadores do vírus da hepatite C, de ambos os gêneros, com média de idade de 51 anos. Foram excluídos do grupo indivíduos com perda auditiva do tipo condutiva ou mista e que apresentassem fatores de risco para perda auditiva. A avaliação foi realizada em dois momentos: antes do uso dos antivirais de ação direta e após o término do tratamento de três meses. Incluiu os seguintes procedimentos: anamnese, inspeção do meato acústico externo, audiometria tonal liminar, limiar de recepção de fala, índice de reconhecimento de fala, medidas de imitância acústica e emissões otoacústicas evocadas por estímulo transiente e produto de distorção. Resultados: Houve baixa ocorrência de zumbido e vertigem. Não houve diferença estatisticamente significativa entre os resultados da avaliação pré-tratamento e pós-tratamento. Conclusão O tratamento com antivirais de ação direta contra o vírus da hepatite C não provocou efeitos adversos na função auditiva.

ABSTRACT Purpose To verify whether treatment with hepatitis C direct-acting antivirals has adverse effects on hearing. Methods The sample consisted of 16 individuals with hepatitis C virus, of both sexes, with an average age of 51 years. Individuals with conductive or mixed hearing loss who presented risk factors for hearing loss were excluded from the group. The evaluation was carried out in two moments: before the use of direct-acting antivirals and after the three-month treatment. It included the following procedures: anamnesis, external auditory canal inspection, pure tone audiometry, speech reception threshold, speech recognition index, acoustic immittance measures and transient and distortion product otoacoustic emissions. Results There was a low incidence of tinnitus and vertigo. There was no statistically significant difference between the results of the pre- and post-treatment assessment. Conclusion The treatment with direct-acting antivirals against the hepatitis C virus did not cause any adverse effects on hearing function.

Estudo das emissões otoacústicas residuais nas perdas auditivas neurossensoriais com diferenciação de artefatos e respostas fisiológicas / Study of residual otoacoustic emissions in hearing loss with artifact differentiation and physiological responses

RESUMO Objetivo avaliar o efeito da variação da intensidade de estimulação sobre as respostas das emissões otoacústicas produto de distorção em indivíduos com perda auditiva neurossensorial, utilizando um protocolo de gradiente de fase das emissões. Métodos estudo observacional transversal. Participaram 38 indivíduos com diagnóstico de perda auditiva neurossensorial de grau leve, moderado ou severo. Foram realizadas anamnese, meatoscopia, audiometria tonal liminar, logoaudiometria, imitanciometria, emissões otoacústicas produto de distorção e emissões otoacústicas residuais. As emissões otoacústicas residuais foram coletadas com o equipamento Echodia, modelo Elios®. O protocolo utilizado permite a variação dos parâmetros frequência e intensidade e as respostas são analisadas por meio do teste do Gradiente de Fase. As respostas registradas nas emissões residuais foram consideradas como "presente", "ausente" e "artefato", considerando a variação da fase em função de f1. Resultados Foram incluídas 72 orelhas. Houve diferença estatisticamente significativa nas frequências de 1300 Hz e 2000 Hz, ao comparar os resultados das emissões residuais. Ao correlacionar o resultado da audiometria e a intensidade de estimulação que evocou a emissão residual, houve correlação positiva para as frequências de 1000 Hz e 4000Hz. O "artefato" foi registrado, principalmente, nas frequências mais agudas: 56,2% em 3000 Hz e 58,2% em 4000 Hz. A emissão otoacústica residual presente foi registrada em 18,6% em 1000 Hz, 13,4% em 2000 Hz, 6,3% em 3000 Hz e 7,5% em 4000 Hz. Conclusão o aumento da intensidade de estimulação no exame de emissões pode auxiliar no estudo das células ciliadas residuais, desde que seja utilizado um protocolo capaz de diferenciar respostas fisiológicas de artefatos.

ABSTRACT Purpose To study the effect of stimulation intensity variation on the responses of distortion products in subjects with sensorineural hearing loss using a new protocol to register the otoacoustic emissions. Methods This is a cross-sectional observational study. The following procedures were performed: anamnesis, otoscopy, pure tone audiometry, speech audiometry, tympanometry, distortion product and residual otoacoustic emissions. The residual DPOAE were collected with the Echodia equipment, Elios®. The protocol that was developed allows the variation of frequency and intensity parameters and the responses are analyzed by phase gradient test. Responses recorded in residual otoacoustic emissions were considered "present", "absent" or "artifact". Results The total included ears was 72. On residual otoacoustic emissions test, at a frequency of 1300Hz and 2000Hz, there was statistically significant difference. By analyzing the average found in the audiometry and the results of residual emissions, only the frequency of 1300Hz showed a statistically significant association in all groups. By correlating the results of the audiometry and the stimulation intensity used to evoke the residual emission, there was positive correlation for the frequencies of 1000Hz and 4000Hz. The "artifact" was mostly recorded in the higher frequencies: 56.2% in 3000Hz and 58.2% in 4000 Hz. Residual EOAPD present was recorded as 18.6% at 1000Hz, 13.4% at 2000Hz, 6.3% at 3000Hz and 7.5% at 4000Hz. Conclusion The increased stimulation intensity in the otoacoustic emissions test can aid in the study of residual outer hair cells, as long as a protocol is used to check the correctness of the responses.

O perfil audiológico e a funcionalidade coclear na síndrome de Williams / Audiological profile and cochlear functionality in Williams syndrome

RESUMO Objetivo avaliar o perfil audiológico e a funcionalidade coclear em indivíduos com SW. Método estudo com 39 indivíduos, sendo 22 indivíduos com SW com idade entre 7 e 17 anos, sendo 15 do sexo masculino e 7 do sexo feminino e 17 indivíduos com desenvolvimento típico e normo-ouvintes. Todos os indivíduos foram avaliados por meio da audiometria tonal limiar, medidas de imitância acústica e análise das Emissões Otoacústicas Transientes (EOAT). Foi avaliado o perfil audiológico dos indivíduos com SW, e também foram comparadas as respostas das EOAT entre os indivíduos com SW sem perda auditiva e indivíduos controles. Resultados perda auditiva foi observada em 50% dos pacientes, sendo 78,95% neurossensorial e 21,05% mista. Esta perda foi predominantemente de grau leve a moderado, acometendo principalmente as frequências a partir de 3 kHz. Quanto às EOAT, observou-se maior incidência de ausência e de respostas de menor amplitude em indivíduos com SW. Conclusão indivíduos com SW apresentam disfunção das células ciliadas, principalmente da região basal da cóclea. Assim, a análise das EOAT é um recurso clínico importante a ser considerada na avaliação audiológica de rotina.

ABSTRACT Purpose to evaluate cochlear functionality in Williams syndrome (WS) individuals. Methods a study with 39 individuals, being 22 with WS aged between 7 and 17 years, 15 male and 7 female, and 17 individuals with typical development and normal hearing. All individuals were evaluated using pure tone audiometry, acoustic immittance measurements, and Transient Evoked Otoacoustic Emissions (TEOAE). The audiological profile in individuals with WS was analyzed, and TEOAE responses were compared between WS individuals without hearing loss and typical developmental individuals. Results The hearing loss was observed in 50% of patients, being 78.95% sensorineural and 21.05% mixed. This hearing loss was predominantly mild to moderate, affecting mainly frequencies above 3 kHz. As for TEOAE, there was a higher incidence of absence and lower amplitude responses in individuals with WS. Conclusion WS individuals have hair cell dysfunction, mainly in the basal region of the cochlea. Thus, TEOAE analysis is an important clinical resource to be considered in the routine audiological evaluation.

Preliminary observation on the differential expression of metformin in preventing noise-induced hearing loss in inner ear protein group of rats / 中华劳动卫生职业病杂志

Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.

Glucose Protects Cochlear Hair Cells Against Oxidative Stress and Attenuates Noise-Induced Hearing Loss in Mice / 神经科学通报·英文版

Oxidative stress is the key determinant in the pathogenesis of noise-induced hearing loss (NIHL). Given that cellular defense against oxidative stress is an energy-consuming process, the aim of the present study was to investigate whether increasing energy availability by glucose supplementation protects cochlear hair cells against oxidative stress and attenuates NIHL. Our results revealed that glucose supplementation reduced the noise-induced formation of reactive oxygen species (ROS) and consequently attenuated noise-induced loss of outer hair cells, inner hair cell synaptic ribbons, and NIHL in CBA/J mice. In cochlear explants, glucose supplementation increased the levels of ATP and NADPH, as well as attenuating H

Manejo del tinnitus con estimulador de sonido con especificidad frecuencial / Treatment of tinnitus with sound stimulator with frequency specificity

Introducción: el tinnitus tiene efectos deletéreos sobre la calidad de vida de un paciente. Cuando la lesión está a nivel coclear, se puede usar acondicionamiento acústico para su tratamiento. Objetivo: determinar el cambio en la percepción del tinnitus antes y después de la intervención terapéutica. Metodología: se planteó un estudio de serie de casos. Pacientes con tinnitus no pulsátil de moderado a catastrófico tratados con estimulador REVE 134™. Se incluyeron pacientes que no mejoraron luego de 3 meses con tratamiento médico. Se les practicó microaudiometría (67 frecuencias) para definir la región coclear afectada. Se excluyeron pacientes con umbrales audiométricos > 60 dB, aquellos con lesiones retrococleares y quienes no desearon participar. Las variables de desenlace fueron Tinnitus Handicap Inventory (THI), escala visual análoga (EVA) y Tinnitus Reaction Questionnaire (TQR), que se midieron pretratamiento y a los 3 y 6 meses postratamiento. Resultados: se incluyeron 11 pacientes (hombres = 5, mujeres = 6). En 5 casos el tinnitus fue bilateral y en 6, unilateral. Los valores pretratamiento fueron THI = 61,4 ± 27,4, EVA = 6,9 ± 2,7 y TQR = 43,2 ± 31,9 (Kolmogorov-Smirnov, p > 0,05). Hubo mejoría estadísticamente significativa con el tratamiento, THI (3 meses = 30,6 ± 21,1; 6 meses = 19 ± 19,2), EVA (3 meses = 5,6 ± 2,3; 6 meses = 3,5 ± 2,0), TQR (3 meses = 25,6 ± 20,0; 6 meses = 14,3 ± 19,9); ANOVA de medidas repetidas (p = 0,007, p = 0,027, p = 0,037; respectivamente). Conclusión: el tratamiento con REVE 134™ fue efectivo en pacientes con tinnitus no pulsátil de moderado a catastrófico.

Introduction: tinnitus can affect the quality of life of a patient. Acoustic stimulation can be used as treatment when the cause of tinnitus is located in the cochlea. Objective: To determine changes in tinnitus perception before and after therapeutic intervention. Methodology: We performed a case series study. Patients with nonpulsatile tinnitus, with no improvement with medical therapy, and moderate to catastrophic grade were treated with the REVE 134™ system. A microaudiometry (67 frequencies) was performed to determine the cochlear regions affected. Patients with auditory thresholds >60 dB, retrocochlear pathologies and who did not want to participate in the study were excluded. The variables studied were Tinnitus Handicap Inventory (THI), Visual Analog Scale (VAS) and Tinnitus Reaction Questionnaire (TQR), that were measured before, three and six months after treatment. Results: 11 patients (male: 5, women: 6) were included. In 5 of them, tinnitus was bilateral and in 6, unilateral. Pretreatment values were: THI = 61.4 ± 27.4, VAS = 6.9 ± 2.7 and TQR = 43.2 ± 31.9 (Kolmogorov-Smirnov, p > 0.05). We found improvement in tinnitus perception with the therapy, and this values had statistical significance (THI: 3rd month = 30.6 ± 21.1; 6th month = 19 ± 19.2), VAS (3rd month = 5.6 ± 2.3; 6th month = 3.5 ± 2.0), TQR (3rd month = 25.6 ± 20.0; 6th month =14.3 ± 19.9); repetitive measures of ANOVA (p = 0.007, p = 0.027, p = 0.037; respectively). Conclusion: Treatment with REVE 134™ was effective in patients with moderate to catastrophic tinnitus.

Design of Scalable Model of Cochlear Scala Tympani / 中国医疗器械杂志

For cochlear implant training and robotic cochlear implant experiments, the design method of scalable scala tympani model was proposed. The mathematical model of the cochlea was used as the central curve of scala tympani channel. Referring to the clinical anatomy data, the contour of the scala tympani cross-section was approximated as an ellipse. The profile was placed along the central curve, and the angle was adjusted to determine the position and orientation of the profile in three dimensions such that the central curve passes through its center. The data was imported into Matlab to generate a three-dimensional mathematical model of scala tympani, which can be expanded by setting different scale factors. The virtual scala tympani model was generated in SolidWorks, and the 2:1 fully transparent scala tympani model were fabricated by 3D printing to replace the specimen for experiment.

The Anatomy and Anatomical Variations of the Round Window Prechamber and Their Implications on Cochlear Implantation: An Anatomical, Imaging, and Surgical Study

Abstract Introduction Over the last decades, there has been a tremendous increase in the number of cochlear implant recipients and, consequently, there is a recent increase of interest in the proper understanding of the anatomy of the round window (RW), which is the most important anatomical land mark during cochlear implant surgery. Objectives The present study was undertaken to assess the detailed surgical and radiological anatomy of the RW prechamber; its shape, directions, measurements, common anatomic variations, and its relationships with different surrounding structures as related to cochlear implantation. Methods A total of 20 cadaveric specimens of human temporal bone were microscopically dissected for the anatomical assessment of the measurements of the RW and its relation to surrounding structures in the tympanum. A total of 20 patients were subjected to cochlear implantation, and a radiological and surgical assessment of the anatomy of their RW prechambers was performed. Results The distances between the RW and the facial canal (FC), the jugular fossa (JF), the carotid canal (CC), and the oval window (OW) were measured. Among the cases subjected to cochlear implantation, the infracochlear tunnel was studied radiologically; the lengths of the anterior and posterior pillars were assessed, and the relation with the direction at which the RW faces was statistically analyzed. Conclusions Proper understanding of the topographic anatomy of the RW, including its direction of opening and the distances from different adjacent structures in the tympanum, is essential for a successful cochlear implantation surgery, since it can help decision-making before the surgery and is useful to avoid many complications, such as misplaced electrode and iatrogenic injury to the surrounding structures.

Otoprotection Mechanisms Against Oxidative Stress Caused by Cisplatin

Abstract Introduction Cisplatin damages the auditory system and is related to the generation of free radicals. Glutathione peroxidase is an endogenous free radicals remover. Objective To investigate the mechanisms involved in otoprotection by N-acetylcys- teine through the expression of glutathione peroxidase in outer hair cells from rats treated with cisplatin. Methods Male Wistar rats were intraperitoneally injected with cisplatin (8 mg/Kg) and/or received oral administration by gavage of N-acetylcysteine (300 mg/Kg) for 3 consecutive days. On the 4th day, the animals were euthanized and beheaded. The tympanic bullae were removed and prepared for scanning electron microscopy and Results Among the groups exposed to ototoxic doses of cisplatin, there was an increase in glutathione peroxidase immunostaining in two groups, the one exposed to cisplatin alone, and the group exposed to both cisplatin and N-acetylcysteine. Conclusion The expression of glutathione peroxidase in the outer hair cells of rats exposed to cisplatin showed the synthesis of this enzyme under cellular toxicity conditions.

Audiological and electrophysiological assessment of professional orchestral musicians / Avaliação audiológica e eletrofisiológica em músicos profissionais de orquestra

ABSTRACT Purpose: to verify whether the frequent musical exposure can impair peripheral and central auditory pathway responses in professional orchestral musicians. Methods: 45 male individuals from 19 to 40 years old participated in the study. They were divided into two groups: one comprising 30 orchestral musicians who played strings or wind instruments, and another with 15 nonmusicians. The two groups were submitted to both conventional and high-frequency pure-tone audiometry, transient-evoked otoacoustic emissions, and frequency-following response. The results were subjected to descriptive and inferential statistical analysis, using the one-way ANOVA unmatched samples parametric test, with a 5% significance level. Results: no significant differences were observed between the hearing thresholds in both conventional and high-frequency audiometry and frequency-following response. However, there were statistically significant differences between transient-evoked otoacoustic emission responses, with lower responses to musicians in comparison to the nonmusician group. Conclusion: the results suggest that frequent musical exposure experienced by orchestral musicians can impair the cochlear hair cells' function. Therefore, audiological monitoring is important to detect subclinical impairments.

RESUMO Objetivo: verificar se a frequente exposição musical é capaz de prejudicar as respostas das vias auditivas periférica e central em músicos profissionais de orquestra. Métodos: participaram 45 indivíduos do sexo masculino, entre 19 e 40 anos, divididos em Grupo de músicos formado por 30 músicos de orquestra que tocavam instrumentos de corda ou de sopro, e Grupo de não músicos formado por 15 indivíduos. Ambos os grupos foram submetidos à audiometria tonal nas frequências convencionais e em altas frequências, Emissões Otoacústicas Transientes e Frequency Following Response. Os resultados foram submetidos à análise estatística descritiva e inferencial, por meio do teste ANOVA One-Way para amostras não pareadas, sendo o nível de significância de 5%. Resultados: não houve diferenças significantes entre os limiares auditivos, tanto nas frequências convencionais quanto nas altas frequências e no Frequency Following Response. No entanto, observou-se diferenças entre as respostas das Emissões Otoacústicas Transientes, sendo que os músicos apresentaram respostas diminuídas em relação ao grupo de não músicos. Conclusão: os resultados sugeriram que a frequente exposição musical que indivíduos que tocam em orquestra vivenciam é capaz de prejudicar a função das células ciliadas da cóclea. Sendo assim, o monitoramento audiológico é importante a fim de detectar alterações subclínicas.

Análise das emissões otoacústicas transitórias por banda de frequência em adolescentes com diabetes mellitus tipo 1 / Transient otoacoustic emissions analysis by frequency bands in adolescents with type 1 diabetes mellitus

Introdução: A associação entre perda auditiva e Diabetes Mellitus tipo 1 (DM1) é ainda pouco estudada. A perda auditiva é uma das complicações crônicas relacionadas ao grau de controle glicêmico, que os pacientes podem apresentar com a progressão da doença. Objetivo: Investigar o comprometimento auditivo por meio das emissões otoacústicas transitórias (EOAT) por banda de frequência em adolescentes com DM1 e relação com o controle glicêmico. Métodos: Foram incluídos 80 adolescentes, 50% do gênero masculino, entre 10 e 19 anos de idade: 40 com DM1 e 40 controles saudáveis, pareados por gênero e idade. Os dados clínicos e laboratoriais foram pesquisados nos prontuários médicos. O controle glicêmico foi avaliado por meio dos exames de hemoglobina glicada e os pacientes com DM1 analisados de acordo com o controle glicêmico. A avaliação auditiva foi realizada por meio da imitanciometria, audiometria, e posteriormente EOAT, em sala tratada acusticamente, pelo protocolo "TE Test" de clique não-linear (1 KHz a 4 kHz) a 80 dB NPS de intensidade (AuDX - Biologic). Resultados: As respostas às EOAT foram ausentes em 5,12% em pacientes com DM1, com diferença significativa em relação aos controles (p=0,04). A análise das EOAT por bandas de frequência mostrou maior proporção de alteração nos adolescentes com DM1 mal controlados quando comparados aos bem controlados, nas frequências de 1000Hz, 2000Hz e 3000Hz (p<0,05). Conclusão: As EOAT por bandas de frequência permitiram a identificação precoce de comprometimento auditivo em adolescentes com DM1 e mostraram associação entre DM1 mal controlado e perda auditiva. (AU)

Introduction: The association between hearing loss and type 1 diabetes mellitus (DM1) is still poorly studied. Hearing loss is one of the chronic complications related to the degree of glycemic control that patients may present with the progression of the disease. Objective: To investigate auditory impairment through transient otoacoustic emissions (TEOAE) by frequency band in adolescents with DM1 and in relation to glycemic control. Methods: Were included 80 adolescents, 50% males, between 10 and 19 years of age: 40 with DM1 and 40 healthy controls, matched by gender and age. Clinical and laboratory data were taken from the medical records. Glycemic control was evalueted by glycated hemoglobin and the patients with DM1 were analyzed according to glycemic control. To the auditory evaluation were used the immittance and audiometry, and the TEOAE. The test was performed in the acoustically treated room, the non-linear TE test protocol (1 KHz to 4 kHz) at 80 dB SPL (AuDX - Biologic ). Results: TEOAE responses were absent in 5.12% of patients with DM1, with a significant difference in relation to controls (p = 0.04). The analysis of TEOAE by frequency bands showed a higher proportion of alteration in adolescents with DM1 poorly controlled when compared to well controlled ones, in the frequencies of 1000Hz, 2000Hz and 3000Hz (p <0.05). Conclusion: TEOAE by frequency bands allowed the early identification of auditory impairment in adolescents with DM1 and showed an association between poorly controlled DM1 and hearing loss. (AU)

Clinical Evidence of Hearing Loss in Patients Treated with Cisplatin for Head-and-Neck Squamous Cell Carcinomas

Background: Cisplatin is a chemotherapeutic agent that is widely used to treat a variety of malignant tumors. Serious doselimiting side effects such as ototoxicity, nephrotoxicity, and neurotoxicity are likely to occur with its use.Aim of the study: The aim of the study was to do audiological evaluation of patients on cisplatin before and after chemotherapyfor squamous cell carcinomas of head and neck and analyze for hearing loss (HL).Materials and Methods: A total of 46 patients undergoing cisplatin administration were included in the study. History taking,preliminary ENT examination, and audiological evaluation with pure-tone audiometry were done. A pure-tone average (PTA) wascalculated using the speech frequencies (500, 1000, and 1500 kHz). High-frequency pure-tone audiometry was also done in allpatients to know the basal auditory threshold before starting cisplatin therapy. Baseline audiometry was done Prior to Chemotherapyor at least 24 h after administration of Cisplatin. Monitoring audiometry was done before each cycle of Cisplatin therapy. Follow-upaudiometry was done 1, 3, and 6 months after chemotherapy. Dosage of cisplatin ranged from 50 mg to 115 mg with cumulativedose ranging from 250 mg to 850 mg in all the patients. All the data were analyzed using standard statistical methods.Observations and Results: Among 46 patients, there were 33 males and 13 females (28.26%) with a male-to-female ratioof 2.53:1. Patients were aged between 45 years and 70 years and the mean age was 55.35 ± 2.70 years. 22/46 (47.82%)patients were in the range of 55–65 years age group followed by 15/46 (32.60%) patients who were in the 45–55 yearsage group. 9/46 (19.56%) patients were in the 65–75 years age group. Patients of all age groups showed high-frequency(3000 kHz–12,000 kHz) HL in the study group. The thresholds were found to be increasing from 35 dB to 59 dB with increasingfrequencies from 3000 kHz to 12,000 kHz.Conclusions: In this study, all the patients showed significant evidence of severe mixed type of HL. The HL was significant inall the age groups and in both the genders. Six months follow-up showed no recovery of HL presumable resulting in permanentHL. Very few patients showed vestibular involvement. Audiometric monitoring may help to provide early evidence of decreasedhearing ability, leading to the possible limitation of the severity of ototoxicity.

Carotid-artery cochlear dehiscence

Changes in course of the internal carotid artery (ICA) are uncommon, and dehiscence of the carotid canal with cochlea may occur. A 48-year-old female individual with pulsatile tinnitus. No other otologic symptoms observed. Otolaryngologic examination and audiometric test with normal results. Computed tomography (CT) scan of the mastoid bones showed dehiscence of cochlea with ICA on the right side. An option for monitored observation was made after analysis of the risks and undefined results of surgery. Patient maintained clinical and audiometric profile. Carotid-artery cochlear dehiscence is a condition that must be known, remembered and investigated, because it may mimic other otologic pathologies. Knowledge about it prevents serious complications that can be difficult to reverse.

The effect of very low dose pulsed magnetic waves on cochlea / Efeito de ondas magnéticas pulsadas de dosagem extremamente baixa na cóclea

Abstract Introduction: In daily life biological systems are usually exposed to magnetic field forces at different intensities and frequencies, either directly or indirectly. Despite negative results, the therapeutic use of the low dose magnetic field has been found in recent studies. The effect of magnetic field forces on cochlear cells is not clear in the literature. Objective: In our study, we first applied in vivo pulsed magnetic fields to laboratory rats to investigate the effects on cochlea with distortion product otoacoustic emission test followed by histopathological examinations. Methods: Twelve rats were included in this study, separated into two groups as study group and control group. The rats in the study group were exposed to 40 Hz pulsed magnetic field for 1 h/day for 30 days; the hearing of the rats was controlled by otoacoustic emission test. Also, their cochleas were removed and histochemical examination was performed by Caspase-3, Caspase-9, and TUNEL methods. Results: A statistically significant difference was determined (p < 0.05) when the hearing thresholds of the groups obtained by using 5714 Hz and 8000 Hz stimuli were compared by Kruskal-Wallis test. A significant reaction was observed in the study group, especially in the outer ciliated cells during immunohistochemical examinations by using Caspase-3 and Caspase-9 methods. A significantly positive difference was determined in the study group, especially at the outer ciliated cells and the support cells of the corti organ, when compared to the control group (p < 0.05) by the TUNEL method. Conclusion: According to the results of our study, the very low dose magnetic field, which is considered to be used for therapeutic purposes recently, can cause both auditory function defects and histopathologic damage in cochlear cells.

Resumo Introdução: Os sistemas biológicos são geralmente expostos a forças de campo magnético em diferentes intensidades e frequências, direta ou indiretamente, na vida diária. Apesar dos resultados negativos, o uso terapêutico do campo magnético de baixa dose tem sido encontrado em estudos recentes. O efeito das forças do campo magnético sobre as células cocleares não está claro na literatura. Objetivo: Em nosso estudo, aplicamos pela primeira vez campos magnéticos pulsados in vivo em ratos de laboratório para investigar os efeitos na cóclea através do teste de emissão otoacústica por produto de distorção e análises histopatológicas. Método: Doze ratos foram incluídos neste estudo, os quais foram separados em dois grupos, grupo de estudo e grupo controle. Os ratos do grupo de estudo foram expostos a campo magnético pulsado de 40 Hz por 1 hora/dia por 30 dias, e a audição dos ratos foi controlada por testes de emissão otoacústica. Além disso, suas cócleas foram colhidas e o exame histoquímico foi feito pelos métodos caspase-3, caspase-9 e TUNEL. Resultados: Foi determinada uma diferença estatisticamente significante (p < 0,05) quando os limiares auditivos dos grupos obtidos por meio dos estímulos de 5714 Hz e 8000 Hz foram comparados pelo teste de Kruskal-Wallis. Uma reação significante foi observada no grupo de estudo, especialmente nas células ciliadas externas nas análises imuno-histoquímicas, com os métodos caspase-3 e caspase-9. Uma diferença significantemente positiva foi determinada no grupo de estudo, especialmente nas células ciliadas externas e nas células de suporte do órgão de Corti, quando comparadas com o grupo controle (p < 0,05) pelo método TUNEL. Conclusão: De acordo com os resultados do nosso estudo, o campo magnético de dose baixa, que tem sido considerado para uso terapêutico recentemente, pode causar defeitos na função auditiva e danos histopatológicos nas células cocleares.

Variations in cochlear size of cochlear implant candidates

Introduction: The cochlear anatomy varies in each individual, and that has an impact on decisions regarding the insertion of electrodes. The measurement of the cochlear size is the routine examination required to choose the proper cochlear implant (CI) electrodes. Objective: To acquire normative data on the size of the cochlea (length, width, height, scala timpani [ST] height, cochlear duct length [CDL]) of CI candidates in Medan, Indonesia. Methods: This descriptive study was conducted based on high-resolution computed tomography (HRCT) temporal bone data and on HRCT temporal data manipulated to reconstruct three-dimensional (3D) multiplanar images with OsiriX MD DICOM Viewer version 9.5.1 (Pixmeo SARL, Bernex, Geneva, Switzerland) viewer of 18 patients (36 ears) who were CI candidates in Medan, Indonesia, in order to determine cochlear length (A), cochlear width, cochlear height, ST height and CDL, calculated through a simple mathematical function. Results: The average cochlear length (A) was 8.75 mm (standard deviation [SD] = 0.31 mm); the average cochlear width was 6.53 mm (SD = 0.35 mm); the average cochlear height was 3.26 mm (SD = 0.24 mm) and the average ST height at the basal cochlea was 1.00 mm (SD = 0.1mm); and 0.71 mm (SD = 0.1 mm) at the half turn of cochlea. The average total CDL was 32.45 mm (SD = 1.31 mm; range: 30.01-34.83 mm). Conclusion: The cochlear size varies in each individual; therefore, the temporal bone measurement of CI candidates using HRCT is essential: for the selection of suitable implant electrodes; to minimize cochlear damages at the insertion of the electrode arrays; and to maximize the hearing improvements (AU)